Cocaine abuse and dependence are chronic, relapsing disorders for which there are few effective treatments. Changes in frontal and sub-cortical neural circuitry following prolonged drug exposure can last for years after cessation and may compromise an addict's ability to suppress drug seeking when exposed to drug- related cues. Attentional Bias Modification (ABM) training purportedly reduces the attentional response to salient drug stimuli and has been shown to be efficacious in treating alcohol dependence; however, the efficacy of ABM in treating individuals with cocaine addiction has yet to be empirically determined. Previous research suggests that chronic cocaine users also exhibit a decreased neuronal response during inhibitory control in addition to the enhanced neuronal response to salient drug cues. Preliminary neuroimaging data obtained during our R03-ISTART grant supports both lines of research, as individuals with cocaine abuse and dependence (CCA) exhibited increased activation in response to realistic cocaine cues and a profound lack of activation during inhibitory control. Although extensive evidence of these two neuronal abnormalities exists, to date we are not aware of a study that has directly compared the differential validity of these two metrics (i.e., enhanced cue reactivity and decreased inhibitory control) for predicting relapse. Additionally, our preliminary data provides evidence of increased intrinsic neuronal activity (functional connectivity; fcMRI) within a frontal sub-cortical circuit in CCA relative to controls. Therefore, the current application has two primary objectives that are both clinically significant and highly innovative. First, we will investigate the efficacy and mechanism of action of ABM in treating cocaine addiction (Aim 1). Second, we will determine which of the three neuronal abnormality or abnormalities (i.e., enhanced cue reactivity or decreased inhibitory control or increased fcMRI) are more predictive of relapse and drug utilization (Exploratory Aim 1). To achieve these two objectives, forty treatment-seeking CCA will be randomized to one of two groups in a blinded fashion: five sessions of ABM treatment or five sessions of a similar categorization control task. All participants will complete an extensive clinical and fMRI battery pre- and post-treatment designed to measure activation during cocaine cue processing, inhibitory control, and functional connectivity. We predict that ABM will prove to be efficacious in reducing relapse and that it will exert its greatest effect on reducing fcMRI and cue reactivity within frontal (orbital frontal cortex and anterior cingulate gyrus) and sub-cortical (ventral striatum) regions implicated in addiction. We also predict that individuals with increased fcMRI within frontal, sub-cortical circuits at baseline will be more likely to relapse, suggesting that repeated exposure to cocaine stimuli may result in changes in the underlying circuitry that are independent of exposure to drug stimuli. The goals of this study are clinically significant as they will potentially provide a new treatment for CCA or, at a minimum, examine whether increased fcMRI, enhanced cue reactivity or decreased inhibitory control are more predictive of relapse. PUBLIC HEALTH RELEVANCE: Chronic cocaine abuse and dependence are associated with major medical, neurological, social and interpersonal complications for the individual, their support network, and society as a whole. There are only a few effective treatments for cocaine abuse and dependence, and the development of more powerful treatments is crucial. Addicts tend to be more sensitive to cues associated with drug use and have a decreased ability to inhibit impulses to use drugs, both of which can be measured using behavioral and neuroimaging techniques such as functional magnetic resonance imaging (fMRI). Attentional Bias Modification (ABM) therapy trains individuals to divert their attention away from cues associated with drug use and has been shown to be effective in alcohol addiction. We will investigate the efficacy of ABM for treating cocaine addiction and use fMRI to identify brain changes associated with treatment effect. We will also identify brain changes that are most predictive of relapse from our collected measures. All of these goals will provide a better understanding of the neurobiological causes of addictive behavior, its chronic relapsing nature, and will contribute directly to finding effective treatments.